Lake Qarun is an inland closed basin, located about 80 Kms south west of Cairo. It suffers from a serious water pollution problem which is due to uncontrolled solid and liquid domestic, in addition to agrochemical contamination and lack of sustainable wastewater management. The present study aimed to follow up the changes in the activities of liver enzymes (ALT, AST, and ALP) in fish (T. zillii and M. capito) Collected from different sites (east, middle and west) of the lake in four seasons. The results showed that in the two fish species at the studied sites, aspartate aminotransferase (AST) activity in the liver showed decreased values in comparison with the control fish samples collected from unpolluted site (fish farm) with percentage ranged between 10.86%-45.56%. Also, alanine aminotransferase (ALT) activity in the liver decreased significantly in comparison with the control fish samples with percentage ranged between 10.23%-54.07%. The alkaline phosphatase (ALP) activity in the liver decreased in comparison with the control fish samples with percentage ranged between 16.34%-49.54%.